Implantable prostheses are commonly used in medical applications. One of the more common prosthetic structures include tubular prostheses which may be used as vascular grafts to replace or repair damaged or diseased blood vessels. To maximize the effectiveness of such a prosthesis, it should be designed with characteristics which closely resemble that of the natural body lumen which it is repairing or replacing.
One form of a conventional tubular prosthesis specifically used for vascular grafts includes a textile tubular structure formed by weaving, knitting, or braiding synthetic fibers into a tubular configuration. Tubular textile structures have the advantage of being naturally porous which allows desired tissue in-growth and assimilation into the body. This porosity, which allows for in-growth of surrounding tissue, must be balanced with fluid tightness so as to minimize leakage during the initial implantation stage.
Attempts to control the porosity of the graft while providing a sufficient fluid barrier have focused on increasing the thickness of the textile structure, providing a tighter stitch construction, and including features such as velours to the graft structure. It is also known to form a prosthesis, especially tubular grafts, from polymers such as polytetrafluoroethylene (PTFE). A tubular graft may be formed by stretching and expanding PTFE into a structure referred to as expanded polytetrafluoroethylene (ePTFE). Grafts formed from ePTFE overcome certain disadvantages inherent in textile grafts, such as that they are more fluid-tight. ePTFE grafts however are not as compliant as textile grafts.
Alternatively, it is also known to apply a natural coating, such as collagen or gelatin to a textile graft in order to render it more blood-tight. Collagen or gelatin impregnation of a graft is another method to render the graft blood-tight. It is desirable that a vascular graft ultimately be sufficiently blood-tight to prevent the loss of blood during implantation, yet also be sufficiently porous to permit in-growth of fibroblast and smooth muscle cells in order to attach the graft to the host tissue and ensure a successful implantation and adaptation within the host body.
Collagen reinforced grafts include collagen obtained from deep flexer tendon of cattle. Tendon derived collagen is generally highly cross-linked and difficult to process by the enzyme digestion procedure described in the patent. The difficulties in processing the collagen lead to increased manufacturing time and expense and decrease commercial viability.
Collagen fibrils may also be mixed with a plasticizer which renders the graft blood-tight. It is preferably done with a Dacron® vascular graft material which may be woven or knit. The collagen source is preferably from bovine skin which has been processed by an acid digestion to result in a fibril dispersion of high purity. The processing steps again are a drawback to the use of collagen coatings.
In addition to the above-mentioned drawbacks associated with collagen, there are also problems relating to the source of the material. Collagen is typically derived from animal sources, primarily from cows. Because of the high demand for resources from cows and other bovines, there is a need to provide an alternate source of biocompatible materials to use for such a coating. Particularly, in light of Bovine Spongiform Encephalopathy, and the threat it poses to cattle worldwide, there is a limited supply of bovine sources.
As an additional alternative, porous vascular graft materials have been pretreated with blood prior to introduction of the graft into the body. Such a pretreatment introduces clotting factors throughout the graft that help to reduce bleeding during surgery by causing blood to become clotted before significant loss of blood to the patient occurs. Generally, these grafts are immersed in, or flushed with, fresh blood of the patient in order to preclot the surfaces of the graft. These methods are limited because they are time consuming, require blood transfusions from the patient, and increase the amount of blood loss from the patient. Thus, such methods are not available in emergency medical situations where the patient has lost a large amount of blood or where time is a critical factor. In addition, such methods cannot be used effectively with patients who are taking anticoagulants, such as heparin or warfarin.
A considerable amount of research has centered around developing materials that are initially blood-tight and then gradually become more porous in order to facilitate healing and tissue ingrowth into the implanted graft. Much of this research has focused on coating the surfaces of porous graft materials with extracellular matrix (ECM) proteins in order to render such graft materials blood-tight, but which, over time biodegrade and promote tissue ingrowth into the graft. As previously stated, collagen, albumin, gelatin, elastin, and fibrin have all been used as bioresorbable sealants for porous vascular grafts.
In addition, gels, hydrogels and sol-gels have also been described as biocompatible, biodegradable materials. A gel is a substance with properties intermediate between the liquid and solid states. Gels deform elastically and recover, yet will often flow at higher stresses. They have extended three-dimensional network structures and are highly porous. Accordingly, many gels contain a very high proportion of liquid to solid. The network structures can be permanent or temporary and are based on polymeric molecules, basically formed from a colloidal solution on standing. Thus, a hydrogel may be described as a gel, the liquid constituent of which is water. By way of contrast, a sol is a colloidal solution, i.e., a suspension of solid particles of colloidal dimensions in a liquid. See, Larouse Directory of Science and Technology 470, 543 (1995).
The bonding of separated tissues together or the coating of the surface of tissues or prosthetic materials to form a water-tight seal is also known. A first protein component is preferably a collagen and a second protein-supporting component that can be a proteoglycan, a saccharide or a polyalcohol. In this composition, the second component is adapted to support the first component by forming a matrix, sol or gel with the first component. Thus, the matrix, sol or gel formed is a hybrid composition that includes a protein component and a protein-supporting component that can be a protein, a saccharide or a polyalcohol. The protein component provides the sealing or bonding function, while the protein-supporting component forms a supporting matrix for the protein.
Hydrogels may be used as wound secretion absorbers or incorporated into wound dressings for absorbing wound secretions. The hydrogel composition of these inventions include 20-70% of at least one multivalent alcohol, for example glycerol, 10-35% of at least one natural biopolymer thickener agent, 0.05-10% of a cross-linking agent and 0-50% of water or physiological saline.
Such hydrogels can be gelatin alone or gelatin in combination with a polysaccharide, particularly an alginate. The hydrogel can be a protein hydrogel or a protein-polysaccharide hybrid hydrogel. In addition to gelatin, collagens and pectins are also preferred protein components in the hydrogel materials. However, protein materials are required to provide the sealing function and the hydrogels are used as carriers for the proteins.
Such hybrid coating compositions are not easily manufactured. For example, the protein components of the hybrid coating compositions can become denatured during the manufacturing, sterilizing or storing of the hydrogel coated material. Once denatured, these hybrid coating compositions can lose their ability to function. Another problem with such hybrid coating compositions is that the surface of the substrate material, e.g., wound dressing or implantable device, must be pretreated with, for example, plasma, in order to effectively bind such compositions to the surface of, for example, a vascular graft. In addition, such hybrid compositions are deposited as coatings on the surface of a substrate material. Such surface coatings are limited in that they are readily accessible to the body's degradative enzymes and thus are swiftly degraded.
There have been attempts to make grafts blood-tight by utilizing substances other than collagen or other proteinaceous material such as by manufacturing a vascular graft impregnated with polysaccharides. This method however requires a chemical or physical pretreatment of the graft in order to modify the graft and make it hydrophilic. The pretreatment of the graft consists of a chemical treatment with sulfuric acid or perchloric acid, or a physical treatment where the fabric surface of the graft is treated with plasma or corona discharge. The goal of the treatment is to make the graft hydrophilic by acquiring an ionic charge, or introducing hydroxyl groups on the fabric surface. After pretreatment, the graft is then coated or impregnated with the polysaccharide. Although this method alleviates the problem of protein denaturation during the manufacturing, sterilizing and storing of, for example, a vascular graft, the surface of such a graft must be chemically or physically altered in order to bind the polysaccharide coating to the surface thereof, for example, by chemically oxidizing the surface of a porous vascular graft with a solution of sulfuric or perchloric acid prior to impregnating the surface of the graft with a polysaccharide solution. Alternatively, the surface of such a graft may be physically altered by pretreatment with plasma or corona discharge. In either case, these methods add additional unnecessary steps to such a process by chemically or physically pretreating the surface of such vascular grafts.
A known bioresorbable sealant composition for an implantable prosthesis includes the combination of at least two polysaccharides which form a hydrogel that imparts a substantially blood-tight barrier to the prosthesis. This requires the combination of at least two polysaccharides, or a polysaccharide and a protein to form a hydrogel.